Diabetes Mellitus Type 2
Conditions
Brief summary
The purpose of this study is to assess the potential of BMS-986036 for treatment obese adults with type-2 diabetes.
Interventions
BIOLOGICALBMS-986036
BIOLOGICALPlacebo (Matching with BMS-986036)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Diagnosed with type-2 diabetes mellitus with HbA1c ≥6.5% to less than 10.0% * Body mass index 30.0 to 50.0
Exclusion criteria
* Any significant acute or chronic medical illness * Inability to self-administer subcutaneous injections * Inability to be venipunctured * Evidence of organ dysfunction beyond what is consistent with the target population * History of allergy to PEGylated compounds or Fibroblast growth factor 21 (FGF21) related compounds
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | Baseline (Day 1) and Week 12 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | Baseline (Day 1) and Week 12 | Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG\*FI)\*(FPG+PG30\*2+PG60\*3+PG120\*2)/8\*(FPI+PI30\*2+PI60\*3+PI120\*2)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60, and 120 minutes after oral glucose load; PI30,60,and 120=plasma insulin levels sampled at 30,60 and 120 minutes after the oral glucose load. |
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Baseline (Day 1) and Week 12 | Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. HOMA-IR is calculated using the following formula's fasting glucose(mg/dL) x fasting insulin(mU/L) / 405. |
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline (Day 1) and Week 12 | The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. QUICKI is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose: 1 / (log(fasting insulin mU/L) + log(fasting glucose mg/dL)). |
| Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | Baseline (Day 1) and Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Plasma Glucose levels over 2 hours were shown as Area Under the Curve, (AUC). |
| Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | Bseline (Day 1) and Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Insulin levels over 2 hours were shown as Area Under the Curve, (AUC). |
| Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | Baseline (Day 1) and Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. C-peptide levels over 2 hours were shown as Area Under the Curve, (AUC). |
| Average Concentration (Cavg) of C-terminal Intact BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | Cavg of C-terminal Intact BMS-986036 was reported. |
| Change in Body Weight From Baseline to Week 12 | Baseline (Day 1) and Week 12 | Change in Body Weight from Baseline to Week 12 as a part of Physical measurement was reported. |
| Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8 | AUC \[0-24 hours, ss\] of C-terminal Intact BMS-986036 was reported. |
| Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of C-terminal Intact BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | AUC \[0-168 hours, ss\] of C-terminal Intact BMS-986036 was reported. |
| Average Concentration (Cavg) of Total BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | Cavg of Total BMS-986036 was reported. |
| Maximum Observed Concentration (Cmax) of Total BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | Maximum observed concentration (Cmax) of Total BMS-986036 was reported. |
| Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8 | AUC \[0-24 hours, ss\] of Total BMS-986036 was reported. |
| Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of Total BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | AUC \[0-168 hours, ss\] of Total BMS- 986036 was reported. |
| Percentage of Participants With ANTI-BMS-986036 Antibody Response | Baseline and Day 126 | Percentage of Participants with ANTI-BMS-986036 Antibody Response (ADA positive and ADA Negative) was reported. Participants were monitored for antibodies to BMS-986036 with an anti-BMS-986036 antibody assay. Titers were reported for samples testing positive in an assay. |
| Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | Maximum observed concentration (Cmax) of C-terminal Intact BMS-986036 was reported. |
Countries
Canada, United States
Participant flow
Pre-assignment details
219 participants were enrolled; 138 entered the lead-in period. Reasons for not entering lead-in period included not meeting study eligibility criteria. 120 were randomized to treatment. Reasons not randomized: 6 withdrew consent, 2 lost to follow-up, 4 no longer met study criteria, 1 due to admin.reason by Sponsor and 4 due to other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: Placebo Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks. | 24 |
| Treatment B: BMS-986036 (1 mg Daily) BMS-986036 1 mg subcutaneous injection once daily for 12 weeks | 24 |
| Treatment C: BMS-986036 (5 mg Daily) BMS-986036 5 mg subcutaneous injection once daily for 12 weeks. | 24 |
| Treatment D: BMS-986036 (20 mg Daily) BMS-986036 20 mg subcutaneous injection once daily for 12 weeks. | 24 |
| Treatment E: BMS-986036 (20 mg Weekly) BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks. | 24 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Subject no longer meets study criteria | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Subject request to discontinue treatment | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment A: Placebo | Total | Treatment E: BMS-986036 (20 mg Weekly) | Treatment D: BMS-986036 (20 mg Daily) | Treatment C: BMS-986036 (5 mg Daily) | Treatment B: BMS-986036 (1 mg Daily) |
|---|---|---|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 7.58 | 56.0 years STANDARD_DEVIATION 9.6 | 55.2 years STANDARD_DEVIATION 12.62 | 56.2 years STANDARD_DEVIATION 8.17 | 55.3 years STANDARD_DEVIATION 9.92 | 55.4 years STANDARD_DEVIATION 9.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 10 Participants | 4 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 15 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 95 Participants | 15 Participants | 20 Participants | 18 Participants | 20 Participants |
| Sex: Female, Male Female | 10 Participants | 53 Participants | 12 Participants | 9 Participants | 11 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 67 Participants | 12 Participants | 15 Participants | 13 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 9 / 24 | 12 / 24 | 7 / 24 | 10 / 24 | 10 / 24 |
| serious Total, serious adverse events | 1 / 24 | 0 / 24 | 0 / 24 | 1 / 24 | 0 / 24 |
Outcome results
Primary
Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported.
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | 0.0005 Percent Change | Standard Deviation 0.00622 |
| Treatment B: BMS-986036 (1 mg Daily) | Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | 0.0029 Percent Change | Standard Deviation 0.00882 |
| Treatment C: BMS-986036 (5 mg Daily) | Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | 0.0007 Percent Change | Standard Deviation 0.00692 |
| Treatment D: BMS-986036 (20 mg Daily) | Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | 0.0004 Percent Change | Standard Deviation 0.00814 |
| Treatment E: BMS-986036 (20 mg Weekly) | Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | -0.0004 Percent Change | Standard Deviation 0.00418 |
Secondary
Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of C-terminal Intact BMS-986036
AUC \[0-168 hours, ss\] of C-terminal Intact BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment D: BMS-986036 (20 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of C-terminal Intact BMS-986036 | 31800 hour*microgram/liter | Geometric Coefficient of Variation 57.6 |
Secondary
Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of Total BMS-986036
AUC \[0-168 hours, ss\] of Total BMS- 986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment D: BMS-986036 (20 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of Total BMS-986036 | 172000 hour*microgram/liter | Geometric Coefficient of Variation 39.1 |
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036
AUC \[0-24 hours, ss\] of C-terminal Intact BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036 | 1210 hour*microgram/liter | Geometric Coefficient of Variation 60.6 |
| Treatment B: BMS-986036 (1 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036 | 4900 hour*microgram/liter | Geometric Coefficient of Variation 50.4 |
| Treatment C: BMS-986036 (5 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036 | 18300 hour*microgram/liter | Geometric Coefficient of Variation 49.2 |
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036
AUC \[0-24 hours, ss\] of Total BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036 | 8200 hour*microgram/liter | Geometric Coefficient of Variation 42.3 |
| Treatment B: BMS-986036 (1 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036 | 37400 hour*microgram/liter | Geometric Coefficient of Variation 44.6 |
| Treatment C: BMS-986036 (5 mg Daily) | Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036 | 153000 hour*microgram/liter | Geometric Coefficient of Variation 43.2 |
Secondary
Average Concentration (Cavg) of C-terminal Intact BMS-986036
Cavg of C-terminal Intact BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Average Concentration (Cavg) of C-terminal Intact BMS-986036 | 50.6 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 60.6 |
| Treatment B: BMS-986036 (1 mg Daily) | Average Concentration (Cavg) of C-terminal Intact BMS-986036 | 204 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 50.4 |
| Treatment C: BMS-986036 (5 mg Daily) | Average Concentration (Cavg) of C-terminal Intact BMS-986036 | 762 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 49.2 |
| Treatment D: BMS-986036 (20 mg Daily) | Average Concentration (Cavg) of C-terminal Intact BMS-986036 | 197 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 60.5 |
Secondary
Average Concentration (Cavg) of Total BMS-986036
Cavg of Total BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Average Concentration (Cavg) of Total BMS-986036 | 342 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 42.3 |
| Treatment B: BMS-986036 (1 mg Daily) | Average Concentration (Cavg) of Total BMS-986036 | 1560 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 44.6 |
| Treatment C: BMS-986036 (5 mg Daily) | Average Concentration (Cavg) of Total BMS-986036 | 6390 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 43.2 |
| Treatment D: BMS-986036 (20 mg Daily) | Average Concentration (Cavg) of Total BMS-986036 | 1130 Microgram per Liter (ug/L) | Geometric Coefficient of Variation 38.9 |
Secondary
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index)
Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG\*FI)\*(FPG+PG30\*2+PG60\*3+PG120\*2)/8\*(FPI+PI30\*2+PI60\*3+PI120\*2)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60, and 120 minutes after oral glucose load; PI30,60,and 120=plasma insulin levels sampled at 30,60 and 120 minutes after the oral glucose load.
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | -0.18 Unit on a scale | Standard Deviation 0.967 |
| Treatment B: BMS-986036 (1 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | -0.19 Unit on a scale | Standard Deviation 1.348 |
| Treatment C: BMS-986036 (5 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | -0.18 Unit on a scale | Standard Deviation 2.102 |
| Treatment D: BMS-986036 (20 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | 0.77 Unit on a scale | Standard Deviation 2.455 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | 0.54 Unit on a scale | Standard Deviation 1.772 |
Secondary
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. HOMA-IR is calculated using the following formula's fasting glucose(mg/dL) x fasting insulin(mU/L) / 405.
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -0.19 Unit on a Scale | Standard Deviation 4.136 |
| Treatment B: BMS-986036 (1 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 0.00 Unit on a Scale | Standard Deviation 5.633 |
| Treatment C: BMS-986036 (5 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -1.88 Unit on a Scale | Standard Deviation 8.94 |
| Treatment D: BMS-986036 (20 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -1.73 Unit on a Scale | Standard Deviation 4.589 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -0.34 Unit on a Scale | Standard Deviation 3.707 |
Secondary
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI)
The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. QUICKI is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose: 1 / (log(fasting insulin mU/L) + log(fasting glucose mg/dL)).
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | 0.00 Unit on a scale | Standard Deviation 0.011 |
| Treatment B: BMS-986036 (1 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | 0.00 Unit on a scale | Standard Deviation 0.01 |
| Treatment C: BMS-986036 (5 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | 0.00 Unit on a scale | Standard Deviation 0.015 |
| Treatment D: BMS-986036 (20 mg Daily) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | 0.00 Unit on a scale | Standard Deviation 0.016 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | 0.00 Unit on a scale | Standard Deviation 0.011 |
Secondary
Change in Body Weight From Baseline to Week 12
Change in Body Weight from Baseline to Week 12 as a part of Physical measurement was reported.
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only subjects with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change in Body Weight From Baseline to Week 12 | -0.22 Kilogram | Standard Deviation 2.615 |
| Treatment B: BMS-986036 (1 mg Daily) | Change in Body Weight From Baseline to Week 12 | -0.26 Kilogram | Standard Deviation 1.718 |
| Treatment C: BMS-986036 (5 mg Daily) | Change in Body Weight From Baseline to Week 12 | -0.10 Kilogram | Standard Deviation 2.883 |
| Treatment D: BMS-986036 (20 mg Daily) | Change in Body Weight From Baseline to Week 12 | -1.09 Kilogram | Standard Deviation 2.583 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change in Body Weight From Baseline to Week 12 | -0.50 Kilogram | Standard Deviation 2.297 |
Secondary
Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. C-peptide levels over 2 hours were shown as Area Under the Curve, (AUC).
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | -0.287 mmol*hr/L | Standard Deviation 1.2463 |
| Treatment B: BMS-986036 (1 mg Daily) | Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | 0.031 mmol*hr/L | Standard Deviation 1.3926 |
| Treatment C: BMS-986036 (5 mg Daily) | Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | -0.181 mmol*hr/L | Standard Deviation 0.8927 |
| Treatment D: BMS-986036 (20 mg Daily) | Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | -0.169 mmol*hr/L | Standard Deviation 1.0176 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | -0.750 mmol*hr/L | Standard Deviation 1.2224 |
Secondary
Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Insulin levels over 2 hours were shown as Area Under the Curve, (AUC).
Time frame: Bseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | -64.648 mmol*hr/L | Standard Deviation 231.6043 |
| Treatment B: BMS-986036 (1 mg Daily) | Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | -72.155 mmol*hr/L | Standard Deviation 277.4819 |
| Treatment C: BMS-986036 (5 mg Daily) | Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | -83.850 mmol*hr/L | Standard Deviation 215.3974 |
| Treatment D: BMS-986036 (20 mg Daily) | Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | -58.313 mmol*hr/L | Standard Deviation 205.1879 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | -150.679 mmol*hr/L | Standard Deviation 257.5965 |
Secondary
Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Plasma Glucose levels over 2 hours were shown as Area Under the Curve, (AUC).
Time frame: Baseline (Day 1) and Week 12
Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | 1.538 Millimole*hour per Liter (mmol*hr/L) | Standard Deviation 4.294 |
| Treatment B: BMS-986036 (1 mg Daily) | Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | 2.594 Millimole*hour per Liter (mmol*hr/L) | Standard Deviation 5.8193 |
| Treatment C: BMS-986036 (5 mg Daily) | Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | -0.646 Millimole*hour per Liter (mmol*hr/L) | Standard Deviation 7.0591 |
| Treatment D: BMS-986036 (20 mg Daily) | Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | -0.215 Millimole*hour per Liter (mmol*hr/L) | Standard Deviation 4.7397 |
| Treatment E: BMS-986036 (20 mg Weekly) | Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | -2.293 Millimole*hour per Liter (mmol*hr/L) | Standard Deviation 4.9322 |
Secondary
Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036
Maximum observed concentration (Cmax) of C-terminal Intact BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | 53.3 microgram/liter | Geometric Coefficient of Variation 61.2 |
| Treatment B: BMS-986036 (1 mg Daily) | Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | 213 microgram/liter | Geometric Coefficient of Variation 50.4 |
| Treatment C: BMS-986036 (5 mg Daily) | Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | 807 microgram/liter | Geometric Coefficient of Variation 48.8 |
| Treatment D: BMS-986036 (20 mg Daily) | Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | 459 microgram/liter | Geometric Coefficient of Variation 41.4 |
Secondary
Maximum Observed Concentration (Cmax) of Total BMS-986036
Maximum observed concentration (Cmax) of Total BMS-986036 was reported.
Time frame: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)
Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Maximum Observed Concentration (Cmax) of Total BMS-986036 | 344 microgram/liter | Geometric Coefficient of Variation 42.5 |
| Treatment B: BMS-986036 (1 mg Daily) | Maximum Observed Concentration (Cmax) of Total BMS-986036 | 1570 microgram/liter | Geometric Coefficient of Variation 44.5 |
| Treatment C: BMS-986036 (5 mg Daily) | Maximum Observed Concentration (Cmax) of Total BMS-986036 | 6440 microgram/liter | Geometric Coefficient of Variation 43.1 |
| Treatment D: BMS-986036 (20 mg Daily) | Maximum Observed Concentration (Cmax) of Total BMS-986036 | 1420 microgram/liter | Geometric Coefficient of Variation 36.1 |
Secondary
Percentage of Participants With ANTI-BMS-986036 Antibody Response
Percentage of Participants with ANTI-BMS-986036 Antibody Response (ADA positive and ADA Negative) was reported. Participants were monitored for antibodies to BMS-986036 with an anti-BMS-986036 antibody assay. Titers were reported for samples testing positive in an assay.
Time frame: Baseline and Day 126
Population: It included all treated participants who were randomized to treatment and subsequently received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Placebo | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Negative | 62.5 Percentage of participants |
| Treatment A: Placebo | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Positive | 37.5 Percentage of participants |
| Treatment B: BMS-986036 (1 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Positive | 79.2 Percentage of participants |
| Treatment B: BMS-986036 (1 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Negative | 16.7 Percentage of participants |
| Treatment C: BMS-986036 (5 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Negative | 12.5 Percentage of participants |
| Treatment C: BMS-986036 (5 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Positive | 83.3 Percentage of participants |
| Treatment D: BMS-986036 (20 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Negative | 37.5 Percentage of participants |
| Treatment D: BMS-986036 (20 mg Daily) | Percentage of Participants With ANTI-BMS-986036 Antibody Response | ADA Positive | 58.3 Percentage of participants |